We carried out the first meta-analysis comparing the technical success and clinical outcomes of endoscopic ultrasound-guided drainage (EUD) and conventional transmural drainage (CTD) for pancreatic pseudocysts. We searched PubMed, Embase, Scopus, and the Cochrane library to identify relevant prospective trials. The technical success rate, short-term (4-6 weeks) success, and long-term (at 6 months) success in symptoms and the radiologic resolution of pseudocysts, complication rates, and death rates were compared. Two eligible randomized-controlled trials and two prospective studies including 229 patients were retrieved. The technical success rate was significantly higher for EUD than for CTD [risk ratio (RR)=12.38, 95% confidence interval (CI): 1.39-110.22]. When CTD failed because of the nonbulging nature of pseudocysts, a crossover was carried out to EUD (n=18), which was successfully performed in all these cases. All patients with portal hypertension and bleeding tendency were subjected to EUD to avoid severe complications. EUD was not superior to CTD in terms of short-term success (RR=1.03, 95% CI: 0.95-1.11) or long-term success (RR=0.98, 95% CI: 0.76-1.25). The overall complications were similar in both groups (RR=0.98, 95% CI: 0.52-1.86). The most common complications were bleeding and infection. There were two deaths from bleeding after CTD. The short-term and long-term treatment success of both methods is comparable only if proper drainage modality is selected in specific clinical situations. For bulging pseudocysts, either EUD or CTD can be selected whereas EUD is the treatment of choice for nonbulging pseudocysts, portal hypertension, or coagulopathy.